A Novel & Tailorable Drug Delivery Device for the Treatment of Periodontitis

一本小说

基本信息

批准号：
7537768
负责人：
DAVID J VACHON
金额：
$ 15.85万
依托单位：
IASIS MOLECULAR SCIENCES, INC
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-13 至 2010-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7537768
关键词：
Address Adult Agonist Anaerobic Bacteria Anti-Inflammatory Agents Anti-inflammatory Antibiotics Binding Biodegradable microsphere Biological Assay Blood Calcium Cardiovascular system Cathepsin G Cerium Charge Chlorhexidine Chronic Clinical Trials Combined Modality Therapy Communicable Diseases Consent Country Cysteine Protease Depth Development Devices Diabetes Mellitus Disease Doxycycline Drug Delivery Systems Drug Formulations Economics Effectiveness Elastases Emulsions Encapsulated Endopeptidases Environment Enzymes Esters Family Gelatinase A Gingivitis Healed Healthcare Hour Hydrolysis In Vitro Individual Intention Ion Exchange Ions Kinetics Liquid substance Liver diseases Lung Matrix Metalloproteinase Inhibitor Matrix Metalloproteinases Microspheres Molecular NIH Program Announcements Neutrophil Collagenase Nucleotides Numbers Nutrient Oils Oral Oral Administration Oral cavity Osteoclasts PGLA PSSO3 Pancreatic Elastase Patients Peptide Antibiotics Peptide Hydrolases Peptide antibodies Peptides Performance Periodontal Diseases Periodontal Pocket Periodontitis Pharmaceutical Preparations Physiological Play Polymers Porosity Porphyromonas gingivalis Potassium Premature Birth Procedures Property Protease Inhibitor Public Health Rate Reactive Oxygen Species Role Salts Science Serine Protease Site Sodium Chloride Source System Systemic disease TNF-alpha converting enzyme Techniques Testing Therapeutic Therapeutic Agents Tissues Tooth Diseases Tooth structure Treatment Protocols United States Food and Drug Administration Vertebral column Virulence Water Work antimicrobial arginyllysine base biomaterial compatibility bone loss cathepsin K controlled release cost cost effective day design falls healing hyperkalemia innovation neutrophil novel pathogen receptor scaling and root planing small molecule social

项目摘要

DESCRIPTION (provided by applicant): This application is directed toward the development of a therapeutic drug conjugates with the intention of providing a cost effective adjunct to scaling and root planing procedures for the reduction of pocket depth in patients with adult periodontitis. This proposed study falls under an existing program announcement (PA-06-085) focusing on the "development of novel delivery systems for rapid and/or sustained, on-demand release of therapeutic agents (e.g., antimicrobial, anti-inflammatory, antibodies, peptides, nucleotides, small molecule receptor agonists/antagonists) in the oral cavity". To this end, the objective of this application will be to formulate and test the ability of several novel derivatives of an existing therapeutic agent that has proven to be effective against neutrophil-derived proteases in early testing, against several known periodontal pathogens and proteases. The major Specific Aims of this work are: 1) to test the effectiveness of the formulations to inhibit facultative anaerobes associated with periodontal disease and 2) to test their effectiveness in inhibiting the activities of bacterial and host-derived proteases that are believed to play major roles in this disease. This innovative and rational design resulted from the idea that addressing multiple biomolecular targets within the periodontal pocket environment should result in a more favorable environment for healing. Thus, the development of a biodegradable, cost-effective microsphere-based treatment for periodontitis that modulates an array of proteases and addresses bacterial burden is the subject of a clinical investigation. Public Health Significance: Periodontal disease is the most common chronic infectious disease in the world. In the U.S., a country known for good oral healthcare, more than 50 percent of adults have gingivitis and 35 percent have periodontitis. Dental disease has both a significant social and economic impact in the U.S. and is estimated to cause 189 million missed hours of work each year and expenses attributed to the disease of more than $60 billion. When the growing evidence that tooth and periodontal disease contributes to other costly systemic diseases such as cardiovascular, pulmonary, digestive and liver diseases, and preterm births, and diabetes are considered, the costs are significantly higher.

描述（由申请人提供）：本申请涉及治疗药物缀合物的开发，旨在为洁治和根面平整手术提供成本有效的辅助手段，以减少成人牙周炎患者的牙周袋深度。这项拟议的研究属于现有计划公告 (PA-06-085)，重点是“开发新型递送系统，用于快速和/或持续、按需释放治疗剂（例如抗菌剂、抗炎剂、抗体、口腔中的肽、核苷酸、小分子受体激动剂/拮抗剂）”。为此，本申请的目的是配制和测试现有治疗剂的几种新型衍生物的能力，这些治疗剂已在早期测试中证明对中性粒细胞衍生的蛋白酶、几种已知的牙周病原体和蛋白酶有效。这项工作的主要具体目标是：1) 测试制剂抑制与牙周病相关的兼性厌氧菌的有效性，2) 测试其抑制细菌和宿主来源的蛋白酶活性的有效性，这些蛋白酶被认为在牙周病中起主要作用。在这种疾病中的作用。这种创新且合理的设计源于这样的想法：解决牙周袋环境中的多个生物分子靶点应该会产生更有利的愈合环境。因此，开发一种可生物降解、经济有效的基于微球的牙周炎治疗方法，调节一系列蛋白酶并解决细菌负担是临床研究的主题。公共卫生意义：牙周病是世界上最常见的慢性传染病。在以良好口腔保健而闻名的美国，超过 50% 的成年人患有牙龈炎，35% 的成年人患有牙周炎。牙科疾病在美国具有重大的社会和经济影响，据估计每年会导致 1.89 亿人误工，并且因该疾病造成的费用超过 600 亿美元。越来越多的证据表明，牙齿和牙周疾病会导致其他昂贵的全身性疾病，如心血管、肺部、消化和肝脏疾病、早产和糖尿病，成本要高得多。